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Sustained Pax6 Expression Generates Primate-like Basal Radial Glia in Developing Mouse Neocortex.

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Sustaining the transcription factor Pax6 in mouse neural progenitors promoted primate-like brain development. This Pax6 function in basal progenitors (BPs) is key to subventricular zone (SVZ) expansion and neocortex evolution.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Evolutionary Biology

Background:

  • Neocortex expansion in mammals correlates with subventricular zone (SVZ) growth and increased basal progenitor (BP) proliferation.
  • Basal radial glia (bRG) are key BPs, and the transcription factor Pax6 is highly expressed in primate BPs but not mouse BPs.

Purpose of the Study:

  • To investigate the role of Pax6 in regulating progenitor behavior and neocortex expansion.
  • To determine if sustained Pax6 expression in mouse basal progenitors can induce primate-like progenitor characteristics.

Main Methods:

  • Conditional expression of Pax6 in embryonic mouse neocortex using a novel Tis21-CreERT2 mouse line and in utero electroporation.
  • Analysis of progenitor behavior, cell-cycle dynamics, and neuron production in wild-type and mutant mouse embryos.
  • Examination of Pax6 expression levels in basal progenitors (BPs) and basal radial glia (bRG) in mouse models.

Main Results:

  • Sustained Pax6 expression in apical radial glia (aRG) and their BP progeny altered cleavage plane orientation, promoting bRG generation.
  • Increased cell-cycle re-entry of BPs and enhanced upper-layer neuron production were observed.
  • Pax6 deficiency reduced the proportion of bRG among BPs, and increased BPs were found in the SVZ and intermediate zone.

Conclusions:

  • Pax6 plays a crucial role in regulating basal progenitor behavior, including bRG generation and proliferation.
  • Sustaining Pax6 function in basal progenitors is a potential mechanism underlying SVZ enlargement and neocortical expansion during evolution.
  • This study identifies specific Pax6 effects in BPs, linking its sustained function to evolutionary increases in brain size.